Oxcarbazepine (10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide) is a 10-keto analogue of carbamazepine (dibenzo[b,f]azepine-5-carboxamide). The structurally similar compounds
are known to block voltage-gated sodium channel activity and indicated for use in the treatment of epilepsy. Oxcarbazepine was designed to avoid the oxidative metabolic transformation of carbamazepine. Oxcarbazepine itself undergoes rapid conversion in vivo to a mixture of (S)-10-hydroxy-10,11-dihydro-5H-dibenzo[b,f]axepine-5-carboxamide (S-licarbazepine or eslicarbazepine) and (R)-10-hydroxy-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide (R-licarbazepine)

Based on the active metabolites of oxcarbazepine, eslicarbazepine acetate, chemically known as (S)-5-carbamoyl-10,11-dihydro-5H-dibenzo[b,f]azepin-10-yl acetate (structure shown below),
was developed on the view that the S-isomer would be a more physiologically effective, have fewer adverse effects, and cross the blood brain barrier more efficiently than R-licarbazepine. Eslicarbazepine acetate prodrug is efficiently absorbed in the gastrointestinal tract and is metabolized to eslicarbazepine by hydrolysis of the acetate group (Rauchenzauner, M. and Luef, G., 2010, Neuropsychiatr Dis Treat. 6: 723-730).
Chemical preparation of eslicarbazepine acetate is described in US2007119197, WO02092572, WO2007117166, WO2007012793, and WO2010113179. One process involves preparing a racemic mixture, resolving the (S) and (R) enantiomers of licarbazepine from the racemic mixture and using the intermediates to form the S- and R-licarbazepine acetate. Another process involves reduction of oxcarbazepine in the presence of a catalyst and a hydride source to form 5-licarbazepine in enantiomeric excess. Eslicarbazepine acetate can also be prepared directly by asymmetric hydrogenation of the enol acetate of oxcarbazepine. See, e.g., WO2007117166.
Publication IPCOM000193904D describes carbonyl reductase (ketoreductase) mediated conversion of oxcarbazepine to S- or R-licarbazepine. The ketoreductases produced either R- or S-licarbazepine in enantiomeric excess, thus indicating differences in stereoselectivity, depending on the type of carbonyl reductase used. The reaction conditions, which included a temperature of 30° C. and time of 18-24 h or a temperature of 40° C. and a time of 18 to 24 h resulted in conversion of only about 6% to about 21% to product (defined as EsCBZ purity).
It is desirable to have efficient and cost-effective processes for synthesis of eslicarbazepine and eslicarbazepine acetate, for example processes that result in conversion of >90% of starting compound to eslicarbazepine in >98% enantiomeric excess. Particularly desirable are efficient processes capable of high percent production of eslicarbazepine with high loading of starting compound (e.g., ≧100 g/L of oxcarbazepine).